Restasis

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WARNINGS

PRECAUTIONS

Potential for Eye Injury and Contamination

To avoid the potential for eye
injury and contamination, be careful not to touch the vial tip to your eye or
other surfaces.

Use with Contact Lenses

RESTASIS® should not be administered while wearing contact lenses.
Patients with decreased tear production typically should not wear contact
lenses. If contact lenses are worn, they should be removed prior to the
administration of the emulsion. Lenses may be reinserted 15 minutes following
administration of RESTASIS® ophthalmic emulsion.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Systemic carcinogenicity studies were carried out in male
and female mice and rats. In the 78-week oral (diet) mouse study, at doses of
1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found
for lymphocytic lymphomas in females, and the incidence of hepatocellular
carcinomas in mid-dose males significantly exceeded the control value.

In the 24-month oral (diet) rat study, conducted at 0.5,
2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded the
control rate in the low dose level. The hepatocellular carcinomas and
pancreatic islet cell adenomas were not dose related. The low doses in mice and
rats are approximately 80 times greater (normalized to body surface area) than
the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming
that the entire dose is absorbed.

Mutagenesis

Cyclosporine has not been found to be mutagenic/genotoxic
in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese
hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the
mouse dominant lethal assay, and the DNA-repair test in sperm from treated
mice. A study analyzing sister chromatid exchange (SCE) induction by
cyclosporine using human lymphocytes in vitro gave indication of a positive
effect (i.e., induction of SCE).

Impairment of Fertility

No impairment in fertility was demonstrated in studies in
male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day
(approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized
to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating.

Use In Specific Populations

Pregnancy

Teratogenic Effects - Pregnancy Category C

Adverse effects were seen in reproduction studies in rats
and rabbits only at dose levels toxic to dams. At toxic doses (rats at 30
mg/kg/day and rabbits at 100 mg/kg/day), cyclosporine oral solution, USP, was
embryo- and fetotoxic as indicated by increased pre- and postnatal mortality
and reduced fetal weight together with related skeletal retardations. These
doses are 5,000 and 32,000 times greater (normalized to body surface area),
respectively, than the daily human dose of one drop (approximately 28 mcL) of
0.05% RESTASIS® twice daily into each eye of a 60 kg person (0.001
mg/kg/day), assuming that the entire dose is absorbed. No evidence of
embryofetal toxicity was observed in rats or rabbits receiving cyclosporine at
oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively, during
organogenesis. These doses in rats and rabbits are approximately 3,000 and
10,000 times greater (normalized to body surface area), respectively, than the
daily human dose.

Offspring of rats receiving a 45 mg/kg/day oral dose of
cyclosporine from Day 15 of pregnancy until Day 21 postpartum, a maternally
toxic level, exhibited an increase in postnatal mortality; this dose is 7,000
times greater than the daily human topical dose (0.001 mg/kg/day) normalized to
body surface area assuming that the entire dose is absorbed. No adverse events
were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the
daily human dose).

There are no adequate and well-controlled studies of RESTASIS® in pregnant women. RESTASIS® should be administered to a
pregnant woman only if clearly needed.

Nursing Mothers

Cyclosporine is known to be excreted in human milk
following systemic administration but excretion in human milk after topical
treatment has not been investigated. Although blood concentrations are
undetectable after topical administration of RESTASIS® ophthalmic
emulsion, caution should be exercised when RESTASIS® is administered
to a nursing woman.

Pediatric Use

The safety and efficacy of RESTASIS® ophthalmic
emulsion have not been established in pediatric patients below the age of 16.

Geriatric Use

No overall difference in safety or effectiveness has been
observed between elderly and younger patients.

Last reviewed on RxList: 6/14/2013
This monograph has been modified to include the generic and brand name in many instances.